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APOE ε2 resilience for Alzheimer's disease is mediated by plasma lipid species: Analysis of three independent cohort studies.
Wang, Tingting; Huynh, Kevin; Giles, Corey; Mellett, Natalie A; Duong, Thy; Nguyen, Anh; Lim, Wei Ling Florence; Smith, Alex At; Olshansky, Gavriel; Cadby, Gemma; Hung, Joseph; Hui, Jennie; Beilby, John; Watts, Gerald F; Chatterjee, Pratishtha; Martins, Ian; Laws, Simon M; Bush, Ashley I; Rowe, Christopher C; Villemagne, Victor L; Ames, David; Masters, Colin L; Taddei, Kevin; Doré, Vincent; Fripp, Jürgen; Arnold, Matthias; Kastenmüller, Gabi; Nho, Kwangsik; Saykin, Andrew J; Baillie, Rebecca; Han, Xianlin; Martins, Ralph N; Moses, Eric K; Kaddurah-Daouk, Rima; Meikle, Peter J.
Afiliação
  • Wang T; Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
  • Huynh K; Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, Victoria, Australia.
  • Giles C; Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
  • Mellett NA; Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, Victoria, Australia.
  • Duong T; Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
  • Nguyen A; Baker Department of Cardiometabolic Health, University of Melbourne, Melbourne, Victoria, Australia.
  • Lim WLF; Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
  • Smith AA; Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
  • Olshansky G; Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
  • Cadby G; Centre for Precision Health, Edith Cowan University, Joondalup, Western Australia, Australia.
  • Hung J; Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
  • Hui J; Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
  • Beilby J; School of Population and Global Health, University of Western Australia, Perth, Western Australia, Australia.
  • Watts GF; Medical School, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia.
  • Chatterjee P; School of Population and Global Health, University of Western Australia, Perth, Western Australia, Australia.
  • Martins I; PathWest Laboratory Medicine of Western Australia, Nedlands, Australia.
  • Laws SM; PathWest Laboratory Medicine of Western Australia, Nedlands, Australia.
  • Bush AI; Medical School, Faculty of Health and Medical Sciences, University of Western Australia, Perth, Western Australia, Australia.
  • Rowe CC; Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Perth, Western Australia, Australia.
  • Villemagne VL; Centre for Precision Health, Edith Cowan University, Joondalup, Western Australia, Australia.
  • Ames D; Department of Biomedical Sciences, Macquarie University, North Ryde, New South Wales, Australia.
  • Masters CL; KaRa Institute of Neurological Disease, Sydney, Macquarie Park, New South Wales, Australia.
  • Taddei K; Centre for Precision Health, Edith Cowan University, Joondalup, Western Australia, Australia.
  • Doré V; Centre for Precision Health, Edith Cowan University, Joondalup, Western Australia, Australia.
  • Fripp J; Collaborative Genomics Group, School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia.
  • Arnold M; Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia.
  • Kastenmüller G; The Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Nho K; The Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Saykin AJ; Department of Molecular Imaging and Therapy, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
  • Baillie R; Department of Molecular Imaging and Therapy, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
  • Han X; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
  • Martins RN; National Ageing Research Institute, Parkville, Victoria, Australia.
  • Moses EK; St George's Hospital, University of Melbourne Academic Unit for Psychiatry of Old Age, Kew, Victoria, Australia.
  • Kaddurah-Daouk R; The Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
  • Meikle PJ; Centre for Precision Health, Edith Cowan University, Joondalup, Western Australia, Australia.
Alzheimers Dement ; 18(11): 2151-2166, 2022 11.
Article em En | MEDLINE | ID: mdl-35077012
ABSTRACT

INTRODUCTION:

The apolipoprotein E (APOE) genotype is the strongest genetic risk factor for late-onset Alzheimer's disease. However, its effect on lipid metabolic pathways, and their mediating effect on disease risk, is poorly understood.

METHODS:

We performed lipidomic analysis on three independent cohorts (the Australian Imaging, Biomarkers and Lifestyle [AIBL] flagship study, n = 1087; the Alzheimer's Disease Neuroimaging Initiative [ADNI] 1 study, n = 819; and the Busselton Health Study [BHS], n = 4384), and we defined associations between APOE ε2 and ε4 and 569 plasma/serum lipid species. Mediation analysis defined the proportion of the treatment effect of the APOE genotype mediated by plasma/serum lipid species.

RESULTS:

A total of 237 and 104 lipid species were associated with APOE ε2 and ε4, respectively. Of these 68 (ε2) and 24 (ε4) were associated with prevalent Alzheimer's disease. Individual lipid species or lipidomic models of APOE genotypes mediated up to 30% and 10% of APOE ε2 and ε4 treatment effect, respectively.

DISCUSSION:

Plasma lipid species mediate the treatment effect of APOE genotypes on Alzheimer's disease and as such represent a potential therapeutic target.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Alzheimer Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans País/Região como assunto: Oceania Idioma: En Revista: Alzheimers Dement Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Austrália
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Alzheimer Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans País/Região como assunto: Oceania Idioma: En Revista: Alzheimers Dement Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Austrália